In this proposal, we will investigate whether environmental factors during pregnancy are related to the likelihood that the offspring will be diagnosed with autism. These factors include infections, immune abnormalities, hormones, and smoking. We aim to address these questions in pregnancies of 1,000 autism cases and 1,000 healthy children using maternal serum samples that were drawn and stored in nearly all pregnancies in Finland from 1987-2007. Children with autism and healthy children matched to the cases on sex, date of birth, birth place and residence in Finland will be identified from detailed national databases that contain diagnoses on nearly all cases of autism in Finland. The serum samples of mothers of autism cases and mothers of healthy controls will be analyzed for these environmental factors. We shall also test whether these maternal environmental factors during pregnancy are related to other pregnancy and birth complications and to abnormalities in growth of the child's head over the first few years of life, prior to the onset of autism. In previous studies, increased head size has been observed in children with autism and this may also be related to development of the illness. For this purpose, we will make use of other large national databases available in nearly all births in Finland. Moreover, we will test whether there are differences in susceptibility to these environmental factors between boys and girls with autism. This study will lay the groundwork for future projects in which we will increase the sample size further, to as many as 5,000 cases of autism, expand the types of risk factors and infant/childhood developmental measures examined, compare effects of risk factors between different subtypes of autism, and assess gene-environment interactions. This research has the potential to result in a better understanding of the different causes of autism and different developmental pathways that can lead to the illness. The discovery of these causes can lead to prevention of cases of autism by improved prenatal care and to the identification of children who are at risk of developing autism. PUBLIC HEALTH RELEVANCE: This work has high public health significance. The identification of prenatal etiologies of autism, and their relationship with other developmental antecedents, has the potential to lead to the eradication of a considerable portion of autism cases through implementable public health measures, such as the administration of influenza vaccination, the prevention of sexually transmitted diseases, thyroid hormone supplementation, and anti-smoking campaigns targeted to pregnant women. Moreover, the research described in this proposal has the potential to facilitate the identification of children at risk for autism and to pathogenic mechanisms by which these early life exposures operate to increase risk for this disorder, which can lead to new modalities of prevention and therapeutic intervention.